PB1810: OUTCOME OF ACUTE MYELOID LEUKEMIA RELAPSE AFTER ALLOGENIC STEM CELL TRANSPLANT: A SINGLE INSTITUTION RETROSPECTIVE STUDY
Authors: C. Castoldi, Y. Hicheri, R. Devillier, M.-A. Hospital, E. D’Incan, S. Garciaz, V. Maisano, C. Saillard, J. Rey, A. Granata, S. Harbi, F. Legrand, S. Furst, D. Blaise, N. Vey
Journal: HemaSphere (2022)

Background: With the advances in allogenic stem cell transplant (Allo-SCT), disease relapse has replaced transplant-related mortality (TRM) as main cause of treatment failure in acute myeloid leukemia (AML). Relapse risk after allo-SCT is about 30%, but is extremely variable depending on clinical and genomic features. The prognostic is very poor, with a 2-year survival rate reported to be less than 20%.There is no standard of care in this situation given the variability in patient’s and disease’s characteristics. In patients with good performance status, intensive chemotherapy can be considered, with subsequent cellular therapy such as donor lymphocyte infusion (DLI) or 2nd allo-SCT. For unfit patients, the main goal is to provide acceptable quality of life. Aims: Our aim is to evaluate the outcome of AML post-transplant relapse. Methods: We presented here a single-institution series of 118 AML patients who relapsed after allo-SCT between January 2009 and December 2019. Results: Median age was 53 (20 – 69) years. 22% of the patients had FLT3 mutation and 53% had adverse genetic risk according to ELN. 79% have been transplanted in CR and 21 % with active disease. Conditioning regimen were myeloablative (MAC) in 39% and reduced intensity (RIC) in 61%. 45% of patients received an allograft from a matched related donor (MRD), 22% from an unrelated donor (MUD), 18% from a haplomismatch related donor, 10% from cord blood cells and 5% from a mismatched unrelated donor (MMURD). 18 patients received prophylactic DLI. 22 developed grade >1 aGVHD, and 23 cGVHD (all grades included). Median time from allo-SCT to relapse was 4.7 months (0.43-88.6). Intensive salvage therapy was used for 28% of the cohort, with a CR rate of 54% and an early mortality of 18%. 64% of patients received non intensive salvage therapy (i.e. demethylating agents, targeted therapies, DLIs…) with a CR rate of 18%. Four of these patients are still alive in CR, all after an association of Azacytidine plus Sorafenib with or without DLI. 8% received supportive care only. Seventeen patients of the cohort underwent a 2nd allo-SCT, 14 in CR (13 after intensive salvage, 1 after non intensive salvage) and 6 with active disease. Conditioning regimen were MAC in 35% and RIC in 65% and 90% of patients had a different donor. Donor was haplomismatch related (60%), MRD (20%), MUD (10%), MMUD (10%). The aGVHD (grade≥1)) and cGVHD (all grades included) rates were respectively 25% and 15%. Early TRM after 2nd allo-SCT was 25%. Four patients (25%) are alive in CR, after intensive salvage treatment and a 2nd allo-SCT in CR. In the whole study group, 1year OS from relapse was 25%, and median OS 5.1months. Factors influencing OS in univariate analyses were Sorror comorbidity score ≥3 at 1st Allo-SCT (1 year OS 17% vs 32%, p=0.036), time to relapse after Allo-SCT < 6months (1 year OS 16% vs 35%, p=0.020), and intensive salvage treatment (1 year OS 33% vs 24%, p=0.019). By multivariate analysis, only PS at relapse (2-3 vs 0.1, HR 1.96, p=0.01) independently influenced OS. Median follow-up (patients alive) was 70.2 (46.3-83.5) months. Summary/Conclusion: Our data are in line with published studies, and confirm the poor outcome of post-transplant relapse. Intensive salvage therapy shows reasonable response rate, but subsequent cellular therapy seems necessary to provide long term disease-free survival. Azacytidine in association with targeted therapy and/or DLI could be an alternative option to achieve remission.